Further insight into the Lewis histo-blood-group system as revealed from study of Polynesian and Caucasian plasma and erythrocyte glycosphingolipids
This project involved the study of Lewis and related blood group glycosphingolipid isolated from individuals with normal and aberrant Lewis/secretor phenotypes. The objective was to find a biochemical basis for the unusual expression of Lewis and secretor phenotypes in Polynesians and to use this information to shed light on the "normal" expression of Lewis antigens. By using purified glycolipids, presenting them in the cell free environment of thin layer chromatography to Lewis antibodies and by determining structures by mass spectrometry it has been shown that: l. The Lec epitope is a terminal Gal?1-3Gal sequence, and not an internal branch as proposed by Hanfland (Hanfland et a1.,1986). 2. Lec or H-5-1 are present in Lewis negative phenotypes and their consequent consumption by the Le and ,Se transferases resulting in the known Lea and Leb antigens can be seen in the Lewis positives. 3. Phenotypically Le(a-b-) individuals have small amounts of Lewis antigens. This clearly demonstrates that although the Lewis negative phenotype exists at the crude serological level, this phenotype is not an "all-or-nothing" phenomenon at the chemical level. This also allows it to be postulated that the le gene is probably partially active. 4. Le(a+b+) individuals have both Lea and Leb glycolipids in the erythrocyte membrane and in plasma. Observed phenotyping anomalies appear to be related to there being quantitatively less Leb-6 in the Polynesian Le(a+b+) erythrocyte membrane than in the Le(a-b+) membrane. 5. The Le(a+b-) phenotype of Polynesians is actually the Le(a+b+) phenotype but with serologically undetectable Leb. This allows it to be postulated that the nonsecretor gene (se) is absent in Polynesians. 6. Extended structures are present in most of the Polynesian samples which is in support of a postulated weak secretor gene (Sew). It now appears that the difference between the extended Lewis glycolipids of Caucasians and Polynesians is quantitative. The postulated, Sew transferase appears to be inefficient and allows for increased formation of elongated glycoconjugates (polyglycosylceramides) to result. 7. Reduced fucosyltransferase activity allows increased elongation of the precursor chain to occur, which allows it to be postulated that fucosylation of the precursor prevents, or at least markedly reduces, chain elongation. It is speculated that, as almost everyone is either Lewis and/or secretor positive, perhaps the prevention of chain elongation is a biological reason as to why the Lewis and Secretor polymorphisms exist. 8. Differences in ceramide patterns of Lewis active glycolipids suggests that the small intestinal tract is not the only origin of plasma glycolipids, or there is differential absorption. 9. There is no plasma glycolipid-based reason for there being increased H type 2 antigen reactivity in the Polynesian erythrocyte membrane, nor a reason for the H antigen association with the Le(a+b+) phenotype.